



UNITED STATES; PATENT ornicn IBERNHABD HEYMANN, 05E mmsnonn-om-tmn-immn, OSKAB DRESSED, 0 E MULHEIM- ON-THE-RHINE, RICHARD KO'IIHE; or VOHVVINIKEL, NEAR ELBERFELD, AND ANTON ossnmmex, or COLOGNE-ON-THE-RHINE. GERMANY, ASSIGNORS TO SYNTHETIC rawnnrsca, 111e,, onnnw Yoa 1v. 2., A CORPORATION osN -w Y RK UREIDS OF SUBSTITUTED AMINONAPHTHDL SUBSTANCES.

No Drawing.

To all whom it may concern:

Be it known that We, BERNHARD HEY- MANN, OSKAR Dnnssnn, RICHARD Korma, and ANTON OssnNBEeK, doctors of philosophy, chemists, citizens of the German Empire, residing at, respectively, \Viesdorf-on-the- Rhine, Miilheim-on-the-Rhine, Vohwinkel, near El'berfeld, and Colognc-on-tl1e-Rliine, Germany, have invented new and useful Improvements in Ureids of Substituted Aminonaphthol Substances, of which the following is a specification.

The. present invention relates to the production of substitution derivatives of 1.8.- aminonaphthol sulfonic acids in the amino group by means of nitro derivatives of the halids of aromatic acids, 6. g. aromatic carboxylic acids, aromatic sulfo acids, etc, reduction to the corresponding amino prod nets, and finally condensation of these substances to ureids.

The above mentioned reduced substitution derivatives of aminonaphtholsulfonic acids may be again substituted by the above acid halids and again reduced before they are condensed to furnish the, ureids.

The ureids of these substituted aminonaphthol sulfonie acids are characterized by containing in their molecule an aggregation of the group:

inwhich R stands for a divalent group containing an acidyl radical, such as CO, the residue of the carboxyl group; S(),, the residue of the sulfonic group; CO CH,:CH, the residue of the cinnan'iic acid; COCH the residue of the Specification of Letters Patent.

Patented J uly 1, 1919.

Application filed March 19, 1914. Serial No, 825,868.

phenylacetic acid, etc; n gives the number of hydrogen atoms left unsubstituted in the naphthalene nucleus; and X substituting groups, such as sulfonic groups; n gives the number of hydrogen atoms left unsnbstituted in the benzene nucleus; and X substituting groups 6, g. Cl, Br, CH OCH etc. They are further characterized by their property of furnishing azodyestuffs when coupled With diazotized anilin, etc. As starting material the 1.8-aminonaphthol sulfouic acids may be employed 6. g, mono-, dior higher sulfonated derivatives. These aminonaphthol substances are substituted by such nitro derivatives of halids of aromatic acids as para-nitro-beuzoyl chlorid of the formula:

/Nog

CsH4 CO CI meta-iiitroanisoyl ehlorid, etc, or by metanitro-benzol-sulfo chlorid of the formula so2 c1 meta-nitro-einnaniyl-chlorid of the formula:

etc.

The reduction of these substituted aminonaphthol snlfonic acids isearried out by means of iron and acetic acid or by any other appropriate method furnishing prodnets of the following general formula:

Finally these amino derivatives of the substituted 1.8-aminonaphthol snh onie acids are treated with phosgen, etc. to furnish the ureids with the following general formula:

0-1: or, as above stated, the acid. halids are repeatedly introduced into the alninonaphthol In the same manner three, four, or still more molecules of the acid halids might be introduced into the aminonaphthol sub stances and correspondingly more complicated substitution derivatives and finally ureids are obtained.

In all these general formulae R stands for a oup containing an acidyl radical.

or the formation of the substituted aminonaphthol substances nitroderivatives of various acid halids may be employed, so that in the general formula last given one R may stand for CO- and the other for S(), or COCH:CH- if nitrobenzoylchlorid, nitrobenZolsulfochlorid or nitrocinnaniylchlorid were used for introduction into the aminonaphthol substance.

The new products possess therapeutic value, as they show strong blood-parasitedcstroying qualities and con'iparatively small injurious efl'ect toward the host They form salts with alkali, alkalin earths or heavy metals 0. 9. Na, Ba, Sr, Cu, Zn, Hg, Ag, which retain the valuable thera peutic properties.

They are also useful in the synthesis of azodyestufi's as they combine with diazotized amins.

In carrying out our process practically we ma proceed as follows Plxample 1: 46 parts of the acid sodium BOIH substances, derivatives of the following genwhich upon treatment with phosgen furnish urelds of the following general formula:

l-nr t-m salt of the substitution derivative obtained from the reaction of para-nitrobenzoylchlorid on 1.8-aminonaphthol-4.6-disulfonic acid and subsequent reduction which has the following constitution:

SO II- l are dissolved in 1000 parts of water and treated with carbonate of soda, until the neutral salt is formed. Then 50 parts of crystallized sodium acetate are added and while stirring phosgen is introduced in a slow current at a temperature of 4045 U. The treatment with phosgen is continued until a test sample shows no reaction with nitrite which means that there is no amino substance present any more. Already during the operation the ureid separates for the greatest part. After the end of the reaction chlorid of sodium added in order to complete the separation. The free acid has the following constitution:

k $0.11 a i tom thol-3.6-disulfonic acid and subsequent reduction which possesses the following formula:

on NH-CO \NHCO SO H- SO:H

are dissolved in about 1000 parts of water and carbonate of soda to form the neutral The neutral sodium salt of this acid after being filtered and dried is a powder which is solulole in Water with yellowish color.

Dilute solutions of this salt also possess strong try panosomes-destroying action. The acid also forms azodycstufl's, when coupled with diazotized anilin.

lution. The new acid obtained has the following formula:

W/CO\ y H on soak /-so,11

Example 3: 50 parts of the acid sodium salt obtained by the action of meta-nitrolienzolsulfochlorid on 1.S aniinonaphthol- 313-disulfonic arid and subsequent reduction which possesses the following formula:

SO H-k are dissolved with water and the required quantity of carbonate of soda to furnish the neutral salt. Then 50 parts of crystallized By dissolvin the same with the addition of carbonate 0 soda and precipitating it by chlorid of sodium the neutral salt is obtained which is easily soluble in water. In the dry form the neutral salt is a faintly reddish powder. It forms azodyes with diazobenzene.

sodium acetate are added and phosgen is introduced as described in Example 1. The thus formed acid has the following formula Example 4: 64.5 parts of the acid sodium salt obtained by the action of ni troanisoyl chlorid on the reduced substituted pderivative obtained from nitroanisoylchl orid and 1.8- a1nin0naphthol-4fi-disulfonic acid and subsequent reduction which possesses the following formula:

are dissolved in water and carbonate of phosgen is introduced as in Example 1. The

soda to form the neutral salt. Then 50 arts new acid thus obtained has the following 5 of crystallized sodium acetate are adde and formula:

The neutral sodium salt in the dry form is the reaction of l'neta-nitrwcinnainyl-chloriil a reddish powder easily soluble in water. on LS-aminonaphtholA.6-disulfonie acid Example 5: 50 parts of the acid salt of and subsequent reduction which has the folthe substitution derivative obtained from lowing constitution:

are dissolved in 1000 parts of water and nitrit which means that there is no amino treated with carbonate of soda, until the substance present an more. Already durneutral salt is formed. Then 50 arts of ing the operation t e ureid separates for crystallized sodium acetate are added and the greatest part. After the end of the while stirring phosgen is introduced in a reaction chlorid of sodium is added in order slow current at a temperature of 4045 C. to complete the separation. The free acid The treatment with phosgen is continued has the following constitution:

until a, test sample shows no reaction with By dissolving the acid by means of carbonate of soda and subsequent addition of chlorid of sodium, the neutral salt of the above acid is precipitated as yellowish powder. Dilute solutions of this substance already possess strongly Spirochteta-derid with the product of the reaction of paranitrocinnamylchlorid on LS-amino-naphtholare dissolved in 1000 parts of water and treated with carboimte of soda, until the neutrai salt is forihcd. Then 50 parts of crystallized sodium carbonate are added and \vhile stirring phosgcn is introduced in a slow eurreht at a lZQlIlPOlfltlll'G of 40 (11. The treatment with phosgen is continued until a test sample shows no reaction with r.6-disulfonic acid and subsequent reduction which has the following constitution;

nitrit which means that thereis no amino substance present any more. Already during the operation the ureid separates for the greatest part. After the end of the reaction chlorid of sodium is added in order to complete the separation. The l re acid has lhc 'lollowing, constitution:

By dissolving the acid by means of carbonate of soda and sub-sequent addition of chlor'id of sodium, the neutral salt of the above acid is preciptated as yellowish powder. The acid, when coupled with diazotized anilin, furnishes a clear red dyestuif.

We claiinz' 1. The recess of producing ureids having valuable" therapeutic properties which co1npriees treatiag with hosgen a naphthalene derivative when molecule contains the following atomic grouping:

in which R stands for, a divalent group rouraining a acid? iradi'cal, n a number less than 7, Xfo r sil st tu f groups, n a number less than i5, and f?" or substituting groups, theaiyl I 'ich is most renucleus, mote from the naphthalene nucleus represented above by C having a free amino attached thereto.

2. he process of producing ureids having valuable therapeutic properties which comprises treating with phosgen a salt of a naphthalene derivative whose molecule contains the following atomic grouping:

50,1103 in which R stands for a divalent group containing an acidyl radical tlke alf'yl, nucleus, which is most remote from e 'n'a hthalene nucleus represented iihtiv'e b'y T1 aving a free amino gmuprattarhed thereto.

4. The process of producing ureids having valuable therapeutic properties which comprises treating with phosgen a salt of a naphthalene derivative Whose molecule contains the following atomic grouping:

in which a stands for a number less than seven, X for substituting groups; the aryl nucleus, which is most remote from ihc naphthalene nucleus represented above by C having a free amino group attached thereto.

5. Theprocess of producing ureids having valuable therapeutic properties which com-- prises treat-in 'with phosgen a salt of a naphthalene derivative whose molecule contains the following atomic grouping:

BO|H(B) the aryl nucleus, which is most remote from the naphthalene nucleus represented above by C having a free amino group attached thereto.

'T. The process of producing ureids having valuable therapeutic properties which comprises treating with phos en a naphthalene derivative having the fol owing formula:

X l in which R stands for a divalent group conforming salts with metals, and forming azodyestufls with diazoti zed anilin, substantially as described. i

Witnesses i.

HA aBRfi LL n j i 1 i copies of this patent: may peohtained l lwi,

mining an acidyl radical, n a number less than seven, X for substituting groups, n a number less than five, and X for substituting groups.

8. The process of producing ureids having valuable therapeutic properties which comprises treating with phosgen a salt of a naphthalene derivarti ve having the following formula:

H t h h-qx in which R stands for a divalent acidyl radical, and n for a number less than seven.

9. The process of producing ureids having valuable therapeutic properties which comprises treating with phosgen a salt of a naphthalene derivative having the following formula: i

one

, Nnm-co c uhnm an H (S nia.

If). The process of producing ureids having valuable therapeutic properties which comprises treating with phosgcn in the presence of sodium acetate at an elevated temperature a salt of a naphthalene derivative having the following formula:

ems

8 )6n in which R stands for a divalent group containing an acidyl radical, n a number less than seven, n a number less than 5, andX for substituting groups.

11. The process of producing ureids having valuable therapeutic properties which comprises treating a solution of sodium para aminobenzo-yl-8.1 amidonaphthol-lfidisulfonate with phosgen in thepresence of sodium acetate at a temperature of about 4045 C.

12. As new products ureids of substituted amino-naphthol substances characterized by the following general formula:

In testimony whereof We have hereunto set our hands in the presence of two subscribing witnesses. p a

BERNHARD HEYMANNm QSK DB'ESSE 1 HIGH RD Ko ANTO cssENBaca,

tcr flve cents each, by addressing the "comm-matches or; Remit wumn tomnc." i i y 

